Anaphylaxis of human lung is accompanied by the synthesis of prostaglandins (PG), including PGF2 alpha and PGE. In an analysis of the tissue source of these prostaglandins, parenchymal preparations of both human and guinea pig (GP) lungs were compared. Peripheral, relatively airway-free preparations of human lung generate PGF2 alpha and PGE in response to histamine and 2-methylhistamine, on H1 agonist, but not to dimaprit, an H2 agonist. GP parenchymal preparations respond in a similar fashion. Stimulation of these same preparations with KCl or carbachol caused no increase in the synthesis of either PG. In human airway preparations all three agonists (histamine, KCl, and carbachol) caused the selective generation of PGE. However, stimulation of GP airway preparations with the agonists caused the production of both PGE and PGF2 alpha. These data indicate that (1) human and GP peripheral lung tissues respond to H1, but not H2, stimulation with the generation of PGF2 alpha and PGE; (2) these parenchymal responses are specific and may not be attributed to muscle contraction; and (3) stimulation of muscle contraction in human airway preparations results in the selective generation of PGE while GP airways produce both PGE and PGF2 alpha.